Realistic simulation of ion flux through membrane sheds light on antibiotic resistance

August 16, 2011

As the gatekeepers of ion flow through cell membranes, ion channels are of key interest in numerous cellular processes. Now, a new study describes an innovative new computational model that realistically simulates the complex conditions found in biological systems and allows for a more accurate look at ion channel function at the level of individual atoms. The research, published by Cell Press in the August 17th issue of the Biophysical Journal, provides a remarkably detailed look at the function of a bacterial channel that kills brain cells in people with bacterial meningitis and provides insight into mechanisms that underlie deadly antibiotic resistance.

"Ion channels play an essential role in cellular homeostasis and signaling," says senior study author, Dr. Ulrich Zachariae, from the Institute for . "The study of their function is crucial both for an understanding of intercellular communication and to develop drugs against a plethora of channel-induced diseases." By developing a new computational model, Dr. Zachariae and colleagues were able to directly simulate ion flux through membrane channels under conditions that closely resembled those experienced by living cells.

The researchers used their new method to study PorB, a bacterial channel that is formed by pathogenic Neisseria meningitidis. PorB inserts into the membranes of key intracellular structures in the infected host and causes them to die. The new approach enabled Dr. Zachariae's group to study detailed molecular mechanisms of ion flux through PorB and to explore the effects of specific mutations on ion passage through the channel. This is medically relevant because these are quick to develop by mutating the PorB channel, which is also the main entrance gate into the bacteria, so that common antibiotics no longer fit through the channel. "A major goal of our research is to determine how common antibiotics should be modified to again pass through bacterial channels," explains Dr. Zachariae.

In summary, the new approach allowed for an extraordinarily meticulous look at ion channel function. "We showed that our method accurately predicted ion conductance and selectivity and elucidated ion conduction mechanisms in great detail," concludes Dr. Zachariae. "Thus we expect it to be useful for studies of the molecular mechanisms of ion passage, such as for the improvement of drug design against ion channel targets like PorB. Results from such studies may prove to be crucial for a large group of dangerous bacterial infections which develop more and more resistance against antibiotics."

Explore further: Scientists propose new method for studying ion channel kinetics

Related Stories

Unraveling the mysteries of poison

April 13, 2006

Researchers from the Max Planck Institite for Biophysical Chemistry and other German and French colleagues have combined magnetic resonance spectroscopy (solid-state NMR) with special protein synthesis procedures to uncover ...

Revolution in understanding of ion channel regulation

January 30, 2008

A study at Rush University Medical Center in Chicago published this week in the online version of Biophysical Journal proposes that bubbles may control the opening and closing of ion channels. This new understanding of the ...

Chloroform provides clue to 150 year old medical puzzle

March 31, 2008

One of the earliest general anaesthetics to be used by the medical profession, chloroform, has shed light on a mystery that’s puzzled doctors for more than 150 years – how such anaesthetics actually work.

Gates open on understanding potassium channel controls

June 3, 2010

Walter and Eliza Hall Institute scientists have made a significant advance in understanding how potassium channels, which permit the flow of electric currents central to many of the body's biological processes, control the ...

Recommended for you

Male seahorse and human pregnancies remarkably alike

September 1, 2015

Their pregnancies are carried by the males but, when it comes to breeding, seahorses have more in common with humans than previously thought, new research from the University of Sydney reveals.

Parasitized bees are self-medicating in the wild, study finds

September 1, 2015

Bumblebees infected with a common intestinal parasite are drawn to flowers whose nectar and pollen have a medicinal effect, a Dartmouth-led study shows. The findings suggest that plant chemistry could help combat the decline ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.